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Development of Novel Galactosylated PLGA Nanoparticles for Hepatocyte Targeting Using Molecular Modelling.

Cláudia D Raposo1, Rita Costa2,3, Krasimira T Petrova1

  • 1LAQV-REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Quinta da Torre, 2829-516 Caparica, Portugal.

Polymers
|January 18, 2020
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Summary

Researchers developed novel doxorubicin-loaded PLGA nanoparticles targeting liver cancer cells (Hep G2) using a galactose-based ligand. This targeted drug delivery system shows promise for effective hepatocyte cancer treatment.

Keywords:
doxorubicin deliverygalactosylated nanoparticleshepatocyte targeting nanoparticlesmolecular modelling for drug targetingsurface modified PLGA nanoparticles

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Area of Science:

  • Biomaterials Science
  • Nanotechnology
  • Drug Delivery Systems

Background:

  • Hepatocellular carcinoma (HCC) remains a significant health challenge, necessitating innovative therapeutic strategies.
  • Targeted drug delivery systems offer improved efficacy and reduced side effects for cancer treatment.
  • Poly(lactic-co-glycolic acid) (PLGA) nanoparticles are a versatile platform for drug encapsulation and delivery.

Purpose of the Study:

  • To design and synthesize novel galactose-based ligands for specific targeting of human hepatoma cells (Hep G2).
  • To develop doxorubicin-loaded PLGA nanoparticles conjugated with the galactose ligand for enhanced liver cancer therapy.
  • To characterize the physicochemical properties and in vitro performance of the targeted nanoparticles.

Main Methods:

  • Molecular docking and quantum chemical calculations were employed to select and design the galactose-based ligand.
  • Bis(1-O-ethyl-β-D-galactopyranosyl)amine ligand was synthesized and conjugated to PLGA.
  • Doxorubicin-loaded PLGA nanoparticles (DOX-PLGA-di-GAL NP) were prepared via emulsion method and characterized.
  • In vitro drug release, cell interaction studies, and cytotoxicity assays were performed using Hep G2 cells.

Main Results:

  • Successfully produced spherical DOX-PLGA-di-GAL NP with a size of 258 ± 47 nm and high drug encapsulation efficiency (83%).
  • In vitro studies confirmed specific interaction of PLGA-di-GAL NP with Hep G2 cells.
  • DOX-PLGA-di-GAL NP demonstrated significant cytotoxicity, reducing Hep G2 cellular viability by approximately 80%.

Conclusions:

  • The developed galactose-ligand-conjugated PLGA nanoparticles show excellent potential for targeted doxorubicin delivery to liver cancer cells.
  • This targeted drug delivery strategy offers a promising approach for improving HCC treatment efficacy.
  • The methodology for designing targeting compounds can be extended to develop drug delivery systems for other organs.